Phosphorus oxybromide → 4-Bromo-2-(2,6-dichloro-4-vinylphenyl)-7-fluoro-2H-pyrazolo[4,3-c]pyridine

HRID 626804Notes

Reaction equation

HRID 626804 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]([CH:8]=[CH2:9])[CH:5]=[C:4]([Cl:10])[C:3]=1[N:11]1[CH:21]=[C:14]2[CH:15]=[N+:16]([O-])[CH:17]=[C:18]([F:19])[C:13]2=[N:12]1.P(Br)(Br)([Br:24])=O>C(Cl)Cl>[Br:24][C:15]1[C:14]2=[CH:21][N:11]([C:3]3[C:2]([Cl:1])=[CH:7][C:6]([CH:8]=[CH2:9])=[CH:5][C:4]=3[Cl:10])[N:12]=[C:13]2[C:18]([F:19])=[CH:17][N:16]=1

Participants

4

Reactant 2

HCID 24613Phosphorus oxybromideHCID 677008712-(2,6-Dichloro-4-vinylphenyl)-7-fluoro-2H-pyrazolo[4,3-c]pyridine 5 oxide

Product 1

HCID 866970824-Bromo-2-(2,6-dichloro-4-vinylphenyl)-7-fluoro-2H-pyrazolo[4,3-c]pyridineYield 25.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

To a suspension of 2-(2,6-dichloro-4-vinylphenyl)-7-fluoro-2H-pyrazolo[4,3-c]pyridine 5 oxide (1.0 g, 3.1 mmol) in DCM (15 mL) under an atmosphere of nitrogen at 0° C., was added phosphorus oxybromide (2.6 g, 9.0 mmol). The reaction mixture was stirred at 0° C. for 1 hour and then allowed to reach room temperature over 30 minutes. The resultant mixture was quenched with saturated aqueous sodium hydrogen carbonate solution and diluted with DCM. The layers were separated and the organic layer was washed with brine, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by silica gel flash chromatography (20% ethyl acetate in cyclohexane) to afford the title compound as a white solid (304 mg, 25% yield). 1H NMR (400 MHz, DMSO-d6): δ 9.41 (d, J=2.5 Hz, 1H), 8.19 (d, J=3.3 Hz, 1H), 7.99 (s, 2H), 6.85 (dd, J=17.6, 11.0 Hz, 1H), 6.25 (d, J=17.6 Hz, 1H), 5.60 (d, J=11.0 Hz, 1H).

Workup

  1. waitto reach room temperature over 30 minutes
  2. customThe resultant mixture was quenched with saturated aqueous sodium hydrogen carbonate solution
  3. additiondiluted with DCM
  4. customThe layers were separated
  5. washthe organic layer was washed with brine
  6. dry with materialdried over anhydrous sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThe residue was purified by silica gel flash chromatography (20% ethyl acetate in cyclohexane)

Sources & evidence

ORD record
ord-fbfdedd603bc4cd3b96cc0125ab29101
Source dataset
uspto-grants-2016_04
Patent number
US09309240B2

Reaction notes

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